4P7E: Triazolopyridine Compounds As Selective Jak1 Inhibitors: From Hit Identification To Glpg0634

Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohn's disease (CD).
PDB ID: 4P7EDownload
MMDB ID: 124857
PDB Deposition Date: 2014/3/27
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4P7E: dimeric; determined by author and by software (PISA)
Molecular Components in 4P7E
Label Count Molecule
Proteins (2 molecules)
Tyrosine-protein Kinase Jak2(Gene symbol: JAK2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB